Bibliographic Details
| Title: |
The Novel Oncolytic Herpes Simplex Virus Type‐1 (HSV‐1) Vaccine Strain VC2 Constitutively Expressing GM‐CSF Causes Increased Intratumoral T Cell Infiltration and Inhibition of Tumor Metastasis in the 4T1/Balb/c Mouse Model of Stage Four Breast Cancer |
| Authors: |
Nabi, Rafiq, Chouljenko, Vladimir N., Musarrat, Farhana, Davis, Megan E., Mohan, Harikrishnan, Ghavimi, Reza, Stanfield, Brent, Dutta, Ojasvi, Kousoulas, Konstantin G. |
| Source: |
Journal of Medical Virology; Feb2025, Vol. 97 Issue 2, p1-11, 11p |
| Abstract: |
Oncolytic virotherapy (OVT) aims to disrupt the tumor microenvironment and provide a unique therapeutic approach against solid tumors. Herpes simplex virus type‐1 (HSV‐1) has shown strong promise for treating various solid tumors and has been approved to treat melanoma and glioma in human patients. Previously, we reported the generation of an engineered HSV‐1 vaccine strain VC2, which has shown exceptional promise as an oncolytic and immunotherapeutic virus. In the present work, we engineered VC2 to constitutively express the murine granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) gene inserted in place of HSV‐1 Glycoprotein C (gC). We tested the efficacy of VC2‐GMCSF for its ability to generate antitumor response in the 4T1 stage four metastatic breast cancer mouse model. GM‐CSF expression enhanced VC2 viral replication and infectious virus production. Tumors formed after 7 days of engraftment in the mammary fat pad of Balb/CJ mice were treated by injecting ~5 × 104 plaque forming units (PFU) of VC2/VC2‐GMCSF once. Intratumor treatment did not appreciably reduce average primary tumor sizes. However, metastatic foci were significantly reduced in mice lungs treated with VC2‐GMCSF compared to VC2 or mock treatment. VC2‐GMCSF intratumoral treatment induced a stronger intratumor T cell infiltration but not an increased cytotoxic activity. A significant T cell infiltration was observed in the metastatic areas in VC2‐GMCSF treated animals, which was associated with reduced pro‐tumor marker PDL1 and VEGF gene expression. These results show that constitutive expression of GM‐CSF enhanced the overall efficacy of VC2 for OVT. VC2‐GMCSF holds promise as oncolytic and immunotherapeutic virotherapy for breast and other cancers. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
